General Information

Hycamtin (topotecan) is a semi-synthetic derivative of
camptothecin and is an anti-tumor drug with topoisomerase
I-inhibitory activity. Topoisomerase I relieves torsional strain in
DNA by inducing reversible single strand breaks. Topotecan binds to
the topoisomerase I-DNA complex and prevents religation of these
single strand breaks.

Hycamtin is specifically indicated for the treatment of relapsed
small cell lung cancer in patients with a prior complete or partial
response and who are at least 45 days from the end of first-line
chemotherapy.

Hycamtin is supplied as a 0.25 mg and 1 mg capsule designed for
oral administration. The recommended initial dose of the drug is
2.3 mg/m2/day once daily for 5 consecutive days, repeated every 21
days. The calculated oral daily dose should be rounded to the
nearest 0.25 mg, and the minimum number of 1 mg and 0.25 mg
capsules should be prescribed. The same number of capsules should
be prescribed for each of the 5 dosing days.

Clinical Results

FDA Approval
FDA approval of Hycamtin was based on the results of a clinical
trial. This randomized, comparative, open label study enrolled 115
subjects who were prior responders (complete or partial) to
firstline chemotherapy, were not considered candidates for standard
intravenous chemotherapy, and had relapsed at least 45 days from
the end of first-line chemotherapy. The subjects received Hycamtin
(2.3 mg/m2/day administered for 5 consecutive days repeated every
21 days) and Best Supportive Care (BSC) or BSC alone. The primary
endpoint was overall survival. Median survival in the Hycamtin arm
was 25.9 weeks (95% CI, 18.3 to 31.6) versus 13.9 weeks (95% CI,
11.1 to 18.6) in the BSC alone arm (log-rank P = .0104).

Side Effects

The side effects associated with the use of Hycamtin may
include, but are not limited to, the following:

Anemia

Leukopenia

Neutropenia

Thrombocytopenia

Nausea

Vomiting

Diarrhea

Mechanism of Action

Hycamtin (topotecan) is a semi-synthetic derivative of
camptothecin and is an anti-tumor drug with topoisomerase
I-inhibitory activity. Topoisomerase I relieves torsional strain in
DNA by inducing reversible single strand breaks. Topotecan binds to
the topoisomerase I-DNA complex and prevents religation of these
single strand breaks. The cytotoxicity of topotecan is thought to
be due to double strand DNA damage produced during DNA synthesis,
when replication enzymes interact with the ternary complex formed
by topotecan, topoisomerase I, and DNA. Mammalian cells cannot
efficiently repair these double strand breaks.